OBJECTIVE—The purpose of this study was to compare an in vivo test of whole-body glycolysis, the deuterated-glucose disposal test (²H-GDT), with insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp and the steady-state plasma glucose (SSPG) test.

RESEARCH DESIGN AND METHODS—The ²H-GDT consists of an oral glucose challenge containing deuterated glucose, followed by measurement of heavy water (²H₂O) production, which represents whole-body glycolytic disposal of the glucose load. ²H₂O production is corrected for ambient insulin concentration as an index of tissue insulin sensitivity. The ²H-GDT was compared with euglycemic-hyperinsulinemic glucose clamps in healthy lean subjects (n = 8) and subjects with the metabolic syndrome (n = 9) and with the SSPG test in overweight (n = 12) and obese (n = 6) subjects.

RESULTS—A strong correlation with the clamp was observed for the 75-g and 30-g ²H-GDT (r = 0.95, P < 0.0001 and r = 0.88, P < 0.0001, respectively). The ²H-GDT and clamp studies revealed marked insulin resistance in subjects with metabolic syndrome compared with lean control subjects. The correlation with the clamp was maintained in each group (lean, r = 0.86, P < 0.01; metabolic syndrome, r = 0.81, P < 0.01) for the 75-g test. The ²H-GDT also correlated strongly with the SSPG test (r = −0.87, P < 0.0001) in overweight and obese subjects.

CONCLUSIONS—The ²H-GDT, which measures whole-body glycolysis in humans in a quantitative manner, correlates highly with the euglycemic-hyperinsulinemic glucose clamp and the SSPG test. Impaired insulin-mediated whole-body glycolysis is a feature of insulin resistance, which provides a means of assessing insulin sensitivity in vivo.